Inhibitors of IMPDH enzyme

The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Inhibitors of IMPDH enzyme

The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Process for making modulators of cystic fibrosis transmembrane conductance regulator

The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

Caspase inhibitors and uses thereof

The present invention provides a compound of formula wherein the variables are as defined herein. The present invention also provides processes for preparing the compounds of formula I, and intermediates thereof, pharmaceutical compositions comprising those compounds, and methods of using the compounds and compositions.

Gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I: or a pharmaceutically acceptable derivative or prodrug thereof. The compounds are useful as inhibitors of bacterial gyrase activity. The present invention also relates to methods for treating bacterial infections in mammala. The present invention also relates to methods for decreasing bacterial quantity in a biological sample.

Inhibitors of IMPDH enzyme

Gyrase inhibitors and uses thereof

CASPASE INHIBITORS AND USES THEREOF

The present invention provides a compound of formula I: wherein the variables are as defined herein. The present invention also provides processes for preparing the compounds of formula I, and intermediates thereof, pharmaceutical compositions comprising those compounds, and methods of using the compounds and compositions.

PROCESSES AND INTERMEDIATES

The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof. 2. The process of claim 1 , wherein the palladium catalyst is Pd(OAc)or Pddba.3. The process of claim 1 , wherein the palladium ligand is phosphine claim 1 , bisphosphine claim 1 , XantPhos claim 1 , DPEPhos claim 1 , or bis(diphenylphosphino)ferrocene.4. The process of claim 3 , wherein the palladium ligand is XantPhos.5. The process of claim 1 , wherein the solvent is toluene claim 1 , dioxane claim 1 , THF claim 1 , or a mixture thereof.6. The process of claim 1 , wherein the base is KCOor CsCO.7. The process of claim 1 , wherein the reaction mixture includes a phase transfer catalyst and optionally water.8. The process of claim 1 , wherein the palladium catalyst is Pd(OAc)or Pddba; the palladium ligand is phosphine claim 1 , bisphosphine claim 1 , XantPhos claim 1 , DPEPhos claim 1 , or bis(diphenylphosphino) ferrocene; the solvent is toluene claim 1 , dioxane claim 1 , THF claim 1 , or a mixture thereof; and the base is KCOor CsCO.10. The process of claim 9 , wherein R is aliphatic claim 9 , aryl claim 9 , or heteroaryl claim 9 , each optionally substituted with 1 to 3 alkyl claim 9 , halo claim 9 , alkoxy claim 9 , —CN claim 9 , —NO claim 9 , —N(R) claim 9 , —SON(R) claim 9 , —NC(O)R claim 9 , —SORor heterocycloalkyl.11. The process of further comprising reducing the compound of formula XXXI to produce a compound of Formula XXX.20. The process of claim 19 , wherein Ris —CHCH.21. The process of claim 20 , wherein Ris a protecting group.22. The process of claim 20 , wherein the protecting group is CBZ.24. The process of claim 23 , wherein the step of purifying the mixture comprises separating the isomers by chromatography.25. The process of claim 23 , wherein the step of purifying the mixture comprises selectively ...

Processes and intermediates

The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.

Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Processes and intermediates

The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.

Inhibitors of IMPDH enzyme

The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I: or a pharmaceutically acceptable derivative or prodrug thereof. The compounds are useful as inhibitors of bacterial gyrase activity. The present invention also relates to methods for treating bacterial infections in mammala. The present invention also relates to methods for decreasing bacterial quantity in a biological sample.

SOLID FORMS OF N-[2,4-BIS(1,1-DIMETHYLETHYL)-5-HYDROXYPHENYL]-1,4-DIHYDRO-4-OXOQUINOLINE-3-CARBOXAMIDE

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Inhibitors of IMPDH enzyme

The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Inhibitors of IMPDH enzyme

The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1, 158-. (canceled)60. The process of claim 59 , wherein PG is propoxy formyl claim 59 , methanesulfonyl claim 59 , 4-nitro-benzoyl claim 59 , ethoxy formyl claim 59 , butoxy formyl claim 59 , t-butoxy formyl claim 59 , i-propoxy formyl or methoxy formyl.61. The process of claim 60 , wherein PG is methoxy formyl.63. The process of claim 62 , wherein the solvent is diethyl ether claim 62 , or methylene chloride.64. The process of claim 63 , wherein the solvent is methylene chloride.67. The process of claim 66 , wherein the reaction is quenched by adding the reaction mixture to cold water.68. The process of claim 66 , wherein the aqueous layer is extracted with dichloromethane.69. The process of claim 68 , wherein the dichloromethane is further washed with water.70. The process of claim 66 , wherein the product is isolated by crystallization with hexane. This application is a continuation of PCT Application No. PCT/US2010/028069 filed Mar. 19, 2010, which claims the priority of U.S. Application No. 61/162,148 filed Mar. 20, 2009; U.S. Application No. 61/246,303 filed Sep. 28, 2009; and U.S. Application No. 61/248,565 filed Oct. 5, 2009, which are hereby incorporated by reference in their entirety.The present invention relates to a process for making modulators of cystic fibrosis transmembrane conductance regulator (“CFTR”).Cystic fibrosis (CF) is a recessive genetic disease that affects approximately 30,000 children and adults in the United States and approximately 30,000 children and adults in Europe. Despite progress in the treatment of CF, there is no cure.CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes an epithelial chloride ion channel responsible for aiding in the regulation of salt and water absorption and secretion in various tissues. Small molecule drugs, known as potentiators that increase the probability of CFTR channel ...

SOLID FORMS OF N-[2,4-BIS(1,1-DIMETHYLETHYL)-5-HYDROXYPHENYL]-1,4-DIHYDRO-4-OXOQUINOLINE-3-CARBOXAMIDE

The present invention relates to solid state forms of N-[2,4-bis(1,1-diethylethyl)-5-hydroxyphenyl]-1,4-dihydro-1-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith. 177.-. (canceled)78. A pharmaceutical pack or kit comprising substantially amorphous N-[2 ,4-bis(1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 ,4-dihydro-4-oxoquinoline-3-carboxamide and a pharmaceutically acceptable carrier.79132.-. (canceled)133. The pharmaceutical pack or kit according to comprising substantially amorphous N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide claim 78 , wherein the substantially amorphous N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide comprises less than about 15% crystalline N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxypheny]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide claim 78 , and a pharmaceutically acceptable carrier.134. The pharmaceutical pack or kit according to claim 78 , wherein the substantially amorphous N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide comprises less than about 5% crystalline N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide claim 78 , and a pharmaceutically acceptable carrier.135. The pharmaceutical pack or kit according to comprising amorphous N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxypheny]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide and a pharmaceutically acceptable carrier. This application claims priority under 35 USC § 119(e) to U.S. Patent Application Ser. No. 60/754,381, filed on Dec. 28, 2005, the entire contents of which are hereby incorporated by reference.The present invention relates to solid state forms, for example, crystalline and amorphous forms, of N-[2,4-bis(1,1- ...

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1, 2. The process of claim 1 , wherein Ris independently —OC(O)OR′ claim 1 , —OC(O)NHR′ claim 1 , or —OC(O)N(R′) claim 1 , wherein R′ is not hydrogen.3. The process of claim 2 , further comprising cleaving the —OC(O)OR′ claim 2 , —OC(O)NHR′ claim 2 , or —OC(O)N(R′)to form —OH.4. The process of claim 3 , wherein the cleavage is performed by treating a compound of Formula 1 with an alcoholic solvent in the presence of NaOH claim 3 , KOH or sodium methoxide.5. The process of claim 4 , wherein the alcoholic solvent is methanol.6. The process of claim 1 , wherein at least one of Ror Ris independently a Cstraight or branched alkyl which is substituted with —COOR′ or —CON(R′) claim 1 , wherein R′ is not hydrogen.7. The process of claim 6 , further comprising hydrolyzing each —COOR′ claim 6 , or —CON(R′)to form —COOH.8. The process of claim 7 , wherein the hydrolysis is performed by treating a compound of Formula 1 with an alcoholic solvent in the presence of NaOH claim 7 , KOH or sodium methoxide.9. The process of claim 8 , wherein the alcoholic solvent is methanol.10. The process of claim 6 , wherein Ris independently —OC(O)OR′ claim 6 , —OC(O)NHR′ claim 6 , or —OC(O)N(R′) claim 6 , wherein R′ is not hydrogen.11. The process of claim 10 , further comprising cleaving the —OC(O)OR′ claim 10 , —OC(O)NHR′ claim 10 , or —OC(O)N(R′)to form —OH.12. The process of claim 11 , wherein the cleavage is performed by treating a compound of Formula 1 with an alcoholic solvent in the presence of NaOH claim 11 , KOH or sodium methoxide.13. The process of claim 12 , wherein the alcoholic solvent is methanol.1413. The process of any of - claims 1 , wherein the coupling is performed in the presence of a base.15. The process of claim 14 , wherein the base is KCO claim 14 , EtN claim 14 , NMM claim 14 , pyridine or DIEA.1615. The process of any of - claims 1 , wherein the coupling is performed in the presence of a ...

Solid forms of N[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I: where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacterial gyrase activity and therefore are useful for treating bacterial infections in mammals.

Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I: where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacterial gyrase activity and therefore are useful for treating bacterial infections in mammals.

Gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I: or a pharmaceutically acceptable derivative or prodrug thereof. The compounds are useful as inhibitors of bacterial gyrase activity. The present invention also relates to methods for treating bacterial infections in mammala. The present invention also relates to methods for decreasing bacterial quantity in a biological sample.

Processes and intermediates

The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.

Gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I:or a pharmaceutically acceptable derivative or prodrug thereof. The compounds are useful as inhibitors of bacterial gyrase activity. The present invention also relates to methods for treating bacterial infections in mammala. The present invention also relates to methods for decreasing bacterial quantity in a biological sample. ...

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1, 2. The process of claim 1 , wherein Ris independently —OC(O)OR′ claim 1 , —OC(O)NHR′ claim 1 , or{'sub': '2', '—OC(O)N(R), wherein R′ is not hydrogen.'}3. The process of claim 2 , further comprising cleaving the —OC(O)OR′ claim 2 , —OC(O)NHR′ claim 2 , or —OC(O)N(R′)to form —OH.4. The process of claim 3 , wherein the cleavage is performed by treating a compound of Formula 1 with an alcoholic solvent in the presence of NaOH claim 3 , KOH or sodium methoxide.5. The process of claim 4 , wherein the alcoholic solvent is methanol.6. The process of claim 1 , wherein at least one of Ror Ris independently a Cstraight or branched alkyl which is substituted with —COOR′ or —CON(R′) claim 1 , wherein R′ is not hydrogen.7. The process of claim 6 , further comprising hydrolyzing each —COOR′ claim 6 , or —CON(R′)to form —COOH.8. The process of claim 7 , wherein the hydrolysis is performed by treating a compound of Formula 1 with an alcoholic solvent in the presence of NaOH claim 7 , KOH or sodium methoxide.9. The process of claim 8 , wherein the alcoholic solvent is methanol.10. The process of claim 6 , wherein Ris independently —OC(O)OR′ claim 6 , —OC(O)NHR′ claim 6 , or —OC(O)N(R′) claim 6 , wherein R′ is not hydrogen.11. The process of claim 10 , further comprising cleaving the —OC(O)OR′ claim 10 , —OC(O)NHR′ claim 10 , or —OC(O)N(R′)to form —OH.12. The process of claim 11 , wherein the cleavage is performed by treating a compound of Formula 1 with an alcoholic solvent in the presence of NaOH claim 11 , KOH or sodium methoxide.13. The process of claim 12 , wherein the alcoholic solvent is methanol.14. The process of claim 1 , wherein the coupling is performed in the presence of a base.15. The process of claim 14 , wherein the base is KCO claim 14 , EtN claim 14 , NMM claim 14 , pyridine or DIEA.16. The process of claim 1 , wherein the coupling is performed in the presence of a solvent.17. The ...

SOLID FORMS OF N-[2,4-BIS(1,1-DIMETHYLETHYL)-5-HYDROXYPHENYL]-1,4-DIHYDRO-4-OXOQUINOLINE-3-CARBOXAMIDE

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith. 1. A method for treating cystic fibrosis in a mammal comprising administering a solid pharmaceutical composition comprising amorphous N-[2 ,4-bis(1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 ,4-dihydro-4-oxoquinoline-3-carboxamide and less than about 30% crystalline N-[2 ,4-bis(1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 ,4-dihydro-4-oxoquinoline-3-carboxamide in combination with an additional therapeutic agent.2. The method of claim 1 , wherein the additional agent is selected from a mucolytic agent claim 1 , a bronchodilator claim 1 , an antibiotic claim 1 , an anti-infective claim 1 , an anti-inflammatory claim 1 , a cystic fibrosis transmembrane conductance regulator (CFTR) modulator claim 1 , and a nutritional agent.3. The method of claim 1 , wherein the composition further comprises a pharmaceutically acceptable excipient.4. The method of claim 1 , wherein the composition is in the form of a solid dispersion.5. The method of claim 1 , wherein the composition comprises less than about 5% claim 1 , based on the composition claim 1 , of crystalline N-[2 claim 1 ,4-bis(1 claim 1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 1 ,4-dihydro-4-oxoquinoline-3-carboxamide.6. The method of claim 1 , wherein the composition further comprises a polymer.7. A method for treating cystic fibrosis in a mammal comprising administering 100% amorphous N-[2 claim 1 ,4-bis(1 claim 1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 1 ,4-dihydro-4-oxoquinoline-3-carboxamide claim 1 , as determined by Cu K alpha radiation (2Θ) X-ray powder diffraction claim 1 , in combination with an additional therapeutic agent.8. The method of claim 7 , wherein the additional therapeutic agent is selected from a mucolytic agent claim 7 , a bronchodilator claim 7 , an antibiotic claim 7 , an anti-infective ...

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1, 158-. (canceled)6058. The compound according to claim , wherein the compound is Compound 32.6158. The compound according to claim , wherein the compound is Compound 33. This application claims priority to three U.S. Provisional Applications having Ser. Nos. 61/162,148, filed on Mar. 20, 2009; 61/246,303, filed on Sep. 28, 2009; and 61/248,565, filed on Oct. 5, 2009. Each of the foregoing Provisional Applications are hereby incorporated by reference in their entirety.The present invention relates to a process for making modulators of cystic fibrosis transmembrane conductance regulator (“CFTR”).Cystic fibrosis (CF) is a recessive genetic disease that affects approximately 30,000 children and adults in the United States and approximately 30,000 children and adults in Europe. Despite progress in the treatment of CF, there is no cure.CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes an epithelial chloride ion channel responsible for aiding in the regulation of salt and water absorption and secretion in various tissues. Small molecule drugs, known as potentiators that increase the probability of CFTR channel opening represent one potential therapeutic strategy to treat CF.Specifically, CFTR is a cAMP/ATP-mediated anion channel that is expressed in a variety of cells types, including absorptive and secretory epithelia cells, where it regulates anion flux across the membrane, as well as the activity of other ion channels and proteins. In epithelia cells, normal functioning of CFTR is critical for the maintenance of electrolyte transport throughout the body, including respiratory and digestive tissue. CFTR is composed of approximately 1480 amino acids that encode a protein made up of a tandem repeat of transmembrane domains, each containing six transmembrane helices and a nucleotide binding domain. The two transmembrane domains are ...

SOLID FORMS OF N-[2,4-BIS(1,1-DIMETHYLETHYL)-5-HYDROXYPHENYL]-1,4-DIHYDRO-4-OXOQUINOLINE-3-CARBOXAMIDE

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith. 110-. (canceled)11. A solid dispersion comprising amorphous N-[2 ,4-bis(1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 ,4-dihydro-4-oxoquinoline-3-carboxamide.12. (canceled)13. (canceled)14. The solid dispersion of claim 11 , further comprising a surfactant claim 11 , polymer claim 11 , or inert pharmaceutically acceptable substance.15. The solid dispersion of claim 11 , further comprising a polymer.16. (canceled)17. (canceled)18. (canceled)19. The solid dispersion of claim 15 , wherein the polymer is hydroxypropylmethylcellulose acetate succinate (HPMCAS).20. (canceled)21. The solid dispersion of claim 15 , wherein the polymer is present in an amount of from about 10% by weight to about 80% by weight.22. The solid dispersion of claim 21 , wherein the polymer is present in an amount of less than about 70% by weight.23. (canceled)24. (canceled)25. The solid dispersion of claim 11 , wherein the N-[2 claim 11 ,4-bis(1 claim 11 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 11 ,4-dihydro-4-oxoquinoline-3-carboxamide is present in an amount of from about 10% by weight to about 80% by weight.26. (canceled)27. (canceled)28. The solid dispersion of claim 11 , further comprising a surfactant.29. The solid dispersion of claim 28 , wherein the surfactant is sodium lauryl sulfate.30. The solid dispersion of wherein the surfactant is present in an amount from about 0.1 to about 5%.31. The solid dispersion of claim 30 , wherein the surfactant is present in 0.5%.32. (canceled)33. (canceled)34. The solid dispersion according to claim 11 , wherein the solid dispersion is obtained by spray drying.35. (canceled)36. (canceled)37. A pharmaceutical composition comprising amorphous N-[2 claim 11 ,4-bis(1 claim 11 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 11 ,4-dihydro-4-oxoquinoline-3- ...

Processes and intermediates

The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.

Gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I:where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacterial gyrase activity and therefore are useful for treating bacterial infections in mammals.

Process for making modulators of cystic fibrosis transmembrane conductance regulator

The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I: or a pharmaceutically acceptable derivative or prodrug thereof. The compounds are useful as inhibitors of bacterial gyrase activity. The present invention also relates to methods for treating bacterial infections in mammala. The present invention also relates to methods for decreasing bacterial quantity in a biological sample.

Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Processes and intermediates

The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.

SOLID FORMS OF N-[2,4-BIS(1,1-DIMETHYLETHYL)-5-HYDROXYPHENYL]-1,4-DIHYDRO-4-OXOQUINOLINE-3-CARBOXAMIDE

The present invention relates to solid state forms of N-[2,4-bis(1,1-diethylethyl)-5-hydroxyphenyl]-1,4-dihydro-1-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith. 177.-. (canceled)78. A pharmaceutical pack or kit comprising substantially amorphous N-[2 ,4-bis(1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 ,4-dihydro-4-oxoquinoline-3-carboxamide and a pharmaceutically acceptable carrier.79132.-. (canceled)133. The pharmaceutical pack or kit according to comprising substantially amorphous N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide claim 78 , wherein the substantially amorphous N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide comprises less than about 15% crystalline N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxypheny]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide claim 78 , and a pharmaceutically acceptable carrier.134. The pharmaceutical pack or kit according to claim 78 , wherein the substantially amorphous N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide comprises less than about 5% crystalline N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide claim 78 , and a pharmaceutically acceptable carrier.135. The pharmaceutical pack or kit according to comprising amorphous N-[2 claim 78 ,4-bis(1 claim 78 ,1-dimethylethyl)-5-hydroxypheny]-1 claim 78 ,4-dihydro-4-oxoquinoline-3-carboxamide and a pharmaceutically acceptable carrier. This application claims priority under 35 USC § 119(e) to U.S. Patent Application Ser. No. 60/754,381, filed on Dec. 28, 2005, the entire contents of which are hereby incorporated by reference.The present invention relates to solid state forms, for example, crystalline and amorphous forms, of N-[2,4-bis(1,1- ...

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1, 2. The process of claim 1 , wherein Ris independently —OC(O)OR′ claim 1 , —OC(O)NHR′ claim 1 , or —OC(O)N(R′) claim 1 , wherein R′ is not hydrogen.3. The process of claim 2 , further comprising cleaving the —OC(O)OR′ claim 2 , —OC(O)NHR′ claim 2 , or —OC(O)N(R′)to form —OH.4. The process of claim 3 , wherein the cleavage is performed by treating a compound of Formula 1 with an alcoholic solvent in the presence of NaOH claim 3 , KOH or sodium methoxide.5. The process of claim 4 , wherein the alcoholic solvent is methanol.6. The process of claim 1 , wherein at least one of Ror Ris independently a Cstraight or branched alkyl which is substituted with —COOR′ or —CON(R′) claim 1 , wherein R′ is not hydrogen.7. The process of claim 6 , further comprising hydrolyzing each —COOR′ claim 6 , or —CON(R′)to form —COOH.8. The process of claim 7 , wherein the hydrolysis is performed by treating a compound of Formula 1 with an alcoholic solvent in the presence of NaOH claim 7 , KOH or sodium methoxide.9. The process of claim 8 , wherein the alcoholic solvent is methanol.10. The process of claim 6 , wherein Ris independently —OC(O)OR′ claim 6 , —OC(O)NHR′ claim 6 , or —OC(O)N(R′) claim 6 , wherein R′ is not hydrogen.11. The process of claim 10 , further comprising cleaving the —OC(O)OR′ claim 10 , —OC(O)NHR′ claim 10 , or —OC(O)N(R′)to form —OH.12. The process of claim 11 , wherein the cleavage is performed by treating a compound of Formula 1 with an alcoholic solvent in the presence of NaOH claim 11 , KOH or sodium methoxide.13. The process of claim 12 , wherein the alcoholic solvent is methanol.1413. The process of any of - claims 1 , wherein the coupling is performed in the presence of a base.15. The process of claim 14 , wherein the base is KCO claim 14 , EtN claim 14 , NMM claim 14 , pyridine or DIEA.1615. The process of any of - claims 1 , wherein the coupling is performed in the presence of a ...

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Process for making modulators of cystic fibrosis transmembrane conductance regulator

The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Inhibitors of IMPDH enzyme

The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Solid Forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith. 1. Solid amorphous N-[2 ,4-bis(1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 ,4-dihydro-4-oxoquinoline-3-carboxamide.2. The solid amorphous N-[2 claim 1 ,4-bis(1 claim 1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 1 ,4-dihydro-4-oxoquinoline-3-carboxamide of claim 1 , comprising less than about 15% crystalline N-[2 claim 1 ,4-bis(1 claim 1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 1 ,4-dihydro-4-oxoquinoline-3-carboxamide.3. A preparation of amorphous N-[2 claim 1 ,4-bis(1 claim 1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 1 ,4-dihydro-4-oxoquinoline-3-carboxamide substantially free of crystalline N-[2 claim 1 ,4-bis(1 claim 1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 1 ,4-dihydro-4-oxoquinoline-3-carboxamide.4. The preparation of claim 3 , further comprising a surfactant claim 3 , polymer claim 3 , or inert pharmaceutically acceptable substance.5. The preparation of or claim 3 , wherein the preparation comprises a solid dispersion claim 3 , a mixture or a liquid dispersion.65. The preparation of one of - claims 3 , wherein the preparation comprises solid particles.76. The preparation of one of - claims 3 , comprising less than about 15% of crystalline N-[2 claims 3 ,4-bis(1 claims 3 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claims 3 ,4-dihydro-4-oxoquinoline-3-carboxamide.87. The preparation of one of - claims 3 , wherein the amorphous N-[2 claims 3 ,4-bis(1 claims 3 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claims 3 ,4-dihydro-4-oxoquinoline-3-carboxamide has a particle size distribution of D10 claims 3 , less than 5 μm.98. The preparation of one of - claims 3 , wherein the amorphous N-[2 claims 3 ,4-bis(1 claims 3 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claims 3 ,4-dihydro-4-oxoquinoline-3-carboxamide have a particle size distribution of D50 claims 3 , less than 17 μm. ...

Processes and Intermediates

The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.

Solid Forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N—[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Inhibitors of IMPDH enzyme

The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Process for Making Modulators of Cystic Fibrosis Transmembrane Conductance Regulator

The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

Process for making modulators of cystic fibrosis transmembrane conductance regulator

The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

Solid forms of N-[2,4-BIS(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Gyrase inhibitors and uses thereof

Disclosed herein are compounds comprising the pharmacophore features HBA, HBD, Grp1, and at least two features selected from Grp2, Grp3 or Grp4: wherein HBA is a hydrogen bond acceptor, HBD is a hydrogen bond donor, and Grps 1-4 are as described in the specification. The compounds are inhibitors of bacterial DNA gyrase and are useful in treating bacterial infections. The pharmacophore features may be used to identify and design new inhibitors.

Inhibitors of IMPDH enzyme

The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Caspase inhibitors and uses thereof

The present invention provides a compound of formula I: wherein the variables are as defined herein. The present invention also provides processes for preparing the compounds of formula I, and intermediates thereof, pharmaceutical compositions comprising those compounds, and methods of using the compounds and compositions.

SOLID FORMS OF N-[2,4-BIS(1,1-DIMETHYLETHYL)-5-HYDROXYPHENYL]-1,4-DIHYDRO-4-OXOQUINOLINE-3-CARBOXAMIDE

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith. 1104-. (canceled)105. A crystal form of N-[2 ,4-bis(1 ,1-dimethylethyl)-5-hydroxyphenyl]-1 ,4-dihydro-4-oxoquinoline-3-carboxamide , characterized by one or more peaks at about 6.2 , about 7.6 , about 12.3 , and about 18.0 degrees in an X-ray powder diffraction pattern obtained using Cu K alpha radiation (2Θ).106. The crystal form of claim 105 , wherein the crystal form of N-[2 claim 105 ,4-bis(1 claim 105 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 105 ,4-dihydro-4-oxoquinoline-3-carboxamide is further characterized by a peak at about 8.40.107. The crystal form of claim 105 , wherein the crystal form of N-[2 claim 105 ,4-bis(1 claim 105 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 105 ,4-dihydro-4-oxoquinoline-3-carboxamide is further characterized by a peak at about 11.0.108. The crystal form of claim 105 , wherein the crystal form of N-[2 claim 105 ,4-bis(1 claim 105 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 105 ,4-dihydro-4-oxoquinoline-3-carboxamide is further characterized by a peak at about 14.8.109. The crystal form of claim 105 , wherein the crystal form of N-[2 claim 105 ,4-bis(1 claim 105 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 105 ,4-dihydro-4-oxoquinoline-3-carboxamide is further characterized by a peak at about 16.1.110. The crystal form of claim 105 , wherein the crystal form of N-[2 claim 105 ,4-bis(1 claim 105 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 105 ,4-dihydro-4-oxoquinoline-3-carboxamide is further characterized by a peak at about 17.1.111. The crystal form of claim 105 , wherein the crystal form of N-[2 claim 105 ,4-bis(1 claim 105 ,1-dimethylethyl)-5-hydroxyphenyl]-1 claim 105 ,4-dihydro-4-oxoquinoline-3-carboxamide is further characterized by a peak at about 18.6.112. The crystal form of claim 105 , wherein the crystal form of ...

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1, 158-. (canceled)60. A compound of Formula 3 , or a pharmaceutically acceptable salt thereof.61. A compound of Formula 4 , or a pharmaceutically acceptable salt thereof. This application claims priority to three U.S. Provisional Applications having Ser. No. 61/162,148, filed on Mar. 20, 2009; 61/246,303, filed on Sep. 28, 2009; and 61/248,565, filed on Oct. 5, 2009. Each of the foregoing Provisional applications are hereby incorporated by reference in their entirety.The present invention relates to a process for making modulators of cystic fibrosis transmembrane conductance regulator (“CFTR”).Cystic fibrosis (CF) is a recessive genetic disease that affects approximately 30,000 children and adults in the United States and approximately 30,000 children and adults in Europe. Despite progress in the treatment of CF, there is no cure.CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes an epithelial chloride ion channel responsible for aiding in the regulation of salt and water absorption and secretion in various tissues. Small molecule drugs, known as potentiators that increase the probability of CFTR channel opening represent one potential therapeutic strategy to treat CF.Specifically, CFTR is a cAMP/ATP-mediated anion channel that is expressed in a variety of cells types, including absorptive and secretory epithelia cells, where it regulates anion flux across the membrane, as well as the activity of other ion channels and proteins. In epithelia cells, normal functioning of CFTR is critical for the maintenance of electrolyte transport throughout the body, including respiratory and digestive tissue. CFTR is composed of approximately 1480 amino acids that encode a protein made up of a tandem repeat of transmembrane domains, each containing six transmembrane helices and a nucleotide binding domain. The two transmembrane domains are ...

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1,

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1,

Inhibitors of impdh enzyme

The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Solid forms of n- [2,4-bis (1,1-dimethylethyl) -5-hydroxyphenyl] -1,4-dihydro-4-oxoquinoline-3-carboxamide

Una dispersión sólida que comprende N-[2,4-bis(1,11-dimetiletilo)-5-hidroxifenilo]-1,4-dihidro-4-oxoquinolina-3-carboxamida amorfa. A solid dispersion comprising amorphous N- [2,4-bis (1,11-dimethylethyl) -5-hydroxyphenyl] -1,4-dihydro-4-oxoquinoline-3-carboxamide.

Process for making modulators of cystic fibrosis transmembrane conductance regulator

Impdh enzyme inhibitor

【課題】新規ＩＭＰＤＨ酵素のインヒビターの提供。 【解決手段】本発明は、ＩＭＰＤＨを阻害する化合物に関する。本発明は、上記化合物を含む医薬組成物にも関する。本発明の化合物及び医薬組成物は、ＩＭＰＤＨ酵素活性を阻害するために特によく適合させており、そしてそれ故、有利には、ＩＭＰＤＨ−仲介過程のための治療剤として使用されうる。本発明は、本発明の化合物及び関連化合物を使用してＩＭＰＤＨの活性を阻害する方法にも関する。 【選択図】なし

GYRASE INHIBITORS AND THEIR USE

Process for making modulators of cystic fibrosis transmembrane conductance regulator

The invention provides processes for the preparation of compounds of the Formula 2, the Formula 40 and the Formula 43: Compounds of the Formula 2, the Formula 40 and the Formula 43 may be used in a process for the preparation of a compound of Formula 1: (see above formula)

Process for Making Modulators of Cystic Fibrosis Transmembrane Conductance Regulator

The invention provides a process for the preparation of a compound of Formula 1, N H (Rx-X H R2 Formula 1 comprising coupling a carboxylic acid of Formula 2 (Rx-X OH Formula 2 with an aniline of Formula 3 Formula 3 in the presence of a coupling agent.

Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Inhibitors of impdh enzyme

Bacterial gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I or a pharmaceutically acceptable derivative thereof. The compounds are useful as inhibitors of bacterial gyrase activity. The present invention also relates to methods for treating bacterial infections in mammals. The present invention also relates to methods for decreasing bacterial quantity in a biological sample.

Inhibitors of impdh enzyme

The present invention relates to compounds of formula (A) which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

SUNFLOWER INHIBITORS AND USES OF THE SAME

Reivindicacion 1: Un método para disminuir la cantidad de bacterias en una muestra biologica, método que comprende la etapa de poner en contacto dicha muestra biologica con un compuesto de formula (1), o una sal farmacéuticamente aceptable del mismo, en donde: Z es O o N- R4; W es nitrogeno o CRa ; Ra es seleccionado entre hidrogeno, halogeno,-CF3, R7, -OR7, o -N(R7)2, R1 es un anillo arilo o heteroarilo, en donde dicho anillo está sustituido opcionalmente por hasta cuatro R9; en donde un sustituyente R9 en la posicion orto de R1 tomado conjuntamente con R2 puede formar un anillo fusionado de 5-8 miembros no saturado o parcialmente no saturado, opcionalmente sustituido, que tiene 0-2 heteroátomos en el anillo seleccionados entre nitrogeno, oxígeno o azufre; R2 y R3 son cada uno seleccionado independientemente entre R6, halogeno, CN, SR6, OR6, N(R6)2, NRCO2R6, NRCON(R6)2, CON(R6)2, NRCOR6, NRN(R6)2, COR6, CO2R6, COCOR6, SO2R6, SO2N(R6)2 o NRSO2R6; o R2 y R3 son tomados conjuntamente para formar un anillo fusionado de 5-8 miembros opcionalmente sustituido, no saturado o parcialmente no saturado, que contiene de 0-2 heteroátomos en el anillo seleccionados entre nitrogeno, oxigeno, o azufre; R4 es seleccionado entre R6, CON(R6), COR6, CO2R6, COCOR6, SO2R6, SO2N(R6)2, o (CH2)yR2; y es 1-6; R5 es seleccionado entre R7, Ar, COAr, CON(R7)Ar, (CH2)yCO2R, (CH2)yN(R7)2, C(=NR10)-NRCOR, C(=S)-N(R7)2, CON(R7)2, CO2R, COR, SO2R, o SO2N(R7)2; Ar es un anillo de cinco miembros heteroarilo, heterociclilo, o carbociclilo, en donde dicho anillo está opcionalmente sustituido por hasta tres sustituyentes seleccionados entre oxo, halogeno, CN, NO2, R8, OR8, NHR8, NHCOR8, NHCONHR8, COR8, CONHR8, SO2R8, NHSO2NHR8 o SO2NHR8; cada R se selecciona independientemente de hidrogeno o un grupo alifático opcionalmente sustituido que tiene de uno a seis carbonos; cada R6 es seleccionado independientemente entre R7 o un grupo opcionalmente sustituido seleccionado entre alcoxi, hidroxialquilo, ...

Processes and intermediates for the preparation of aspartic acetal caspase inhibitors

Processes and intermediates for the preparation of aspartic acetal caspase inhibitors Abstract The invention relates to processes such as that shown in the scheme and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde s moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.

Inhibitors of impdh enzyme

The present invention relates to compounds of formula (A) which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Bacterial gyrase inhibitors and uses thereof

THE PRESENT INVENTION RELATES TO COMPOUNDS OF THE FORMULA I:I OR A PHARMACEUTICALLY ACCEPTABLE DERIVATIVE OR PRODRUG THEREOF. THE COMPOUNDS ARE USEFUL AS INHIBITORS OF BACTERIAL GYRASE ACTIVITY. THE PRESENT INVENTION ALSO RELATES TO METHODDS FOR TREATING BACTERIAL INFECTIONS IN MAMMALA. THE PRESENT INVENTION ALSO RELATES TO METHODS FOR DECREASING BACTERIAL QUANTITY IN A BIOLOGICAL SAMPLE.

Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

Caspase inhibitors and uses thereof

The present invention provides a compound of formula (I): wherein the variables are as defined herein. The present invention also provides processes for preparing the compounds of formula (I), and intermediates thereof, pharmaceutical compositions comprising those compounds, and methods of using the compounds and compositions. (see formula I)

Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1 ,1 -dimethylethyl)-5 hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Caspase inhibitors and uses thereof

The present invention provides a compound of formula (I): wherein the variables are as defined herein. The present invention also provides processes for preparing the compounds of formula (I), and intermediates thereof, pharmaceutical compositions comprising those compounds, and methods of using the compounds and compositions.

Processes and intermediates for the preparation of aspartic acetal caspase inhibitors

The invention relates to processes such as that shown in the scheme and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.

Processes and intermediates for the preparation of aspartic acetal caspase inhibitors

Processes and intermediates for the preparation of aspartic acetal caspase inhibitors Abstract The invention relates to processes such as that shown in the scheme and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde s moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.

PROCEDURE FOR MANUFACTURING MODULATORS OF CFTR REGULATOR

The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

Process for making modulators of cystic fibrosis transmembrane conductance regulator

Process for making modulators of cystic fibrosis transmembrane conductance regulator

Process for making modulators of cystic fibrosis transmembrane conductance regulator

The invention provides a process for the preparation of a compound of Formula 1; comprising coupling a carboxylic acid of Formula 2; with an aniline of Formula 3; in the presence of a coupling agent.

SUNFLOWER INHIBITORS AND THEIR USES.

El uso de un compuesto que tiene la fórmula: o de una de sus sales farmacéuticamente aceptables, fórmula en la que R1 es un grupo opcionalmente sustituido, seleccionado entre un grupo alifático(C1-C6), - C(R4)2(CH2)nNRCOR, -C(R4)=N-OR, -C(R4)=N-OC(=O)(grupo alifático(C1-C6)), -C(R4)=NNRCO2(grupo alifático(C1-C6)), -C(R4)=NNRCOR, -C(R4)=NN(R)2, -C(R4)2(CH2)nNRCO2(grupo alifático(C1-C6)), -CO2(grupo alifático(C1-C6)), -CON(R)2, - C(R4)2(CH2)nCON(R)2, -C(R4)2(CH2)nSO2N(R)2, -CONH-OR, - SO2N(R)2, o -C(R4)2(CH2)nNRSO2(grupo alifático C1-C6)); n es cero o uno; cada R se selecciona independientemente entre hidrógeno o un grupo alifático(C1-C6) opcionalmente sustituido; R2 se selecciona entre hidrógeno o, cuando R1 es -CO2(grupo alifático(C1-C3)) o -CONH(grupo alifático(C1- C3)), R2 se selecciona además entre -halo, -CN, -grupo alifático(C1-C4), un heterociclilo de tres a cinco miembros, o un heteroarilo de cinco miembros; el Anillo A es un anillo de heteroarilo seleccionado entre tiazol, oxazol, imidazol o pirazol, en el que dicho imidazol está opcionalmente unido por medio de un puente(C1-C3) desde un nitrógeno del anillo de imidazol a un Ar para formar un anillo fusionado de cinco a siete miembros; Z es C-R3 o N-R3; R3 es -(CH2)pN(R5)2 o un grupo opcionalmente sustituido, seleccionado entre un grupo alifático(C1-C8), heterociclilo, heterociclilalquilo, arilo, aralquilo, heteroarilo o heteroaralquilo; cada R4 se selecciona independientemente entre hidrógeno, un grupo alifático(C1-C6) opcionalmente sustituido, o dos R4, considerados junto con el carbono al que están unidos, forman un anillo alifático de tres a seis miembros; cada R5 se selecciona independientemente entre hidrógeno, un grupo alifático(C1-C4) opcionalmente sustituido, o dos R5, considerados junto con el nitrógeno al que están unidos, forman un anillo heterocíclico de cinco o seis miembros; p es un número entero de cero a cuatro cuando Z es C-R3, o un número entero de uno a cuatro cuando Z es N- R3; y Ar es ...

Caspase inhibitors and uses thereof

The present invention provides a compound of formula (I): wherein the variables are as defined herein. The present invention also provides processes for preparing the compounds of formula (I), and intermediates thereof, pharmaceutical compositions comprising those compounds, and methods of using the compounds and compositions.

Gyrase inhibitors and uses thereof

The present invention relates to compounds of the formula I:where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacterial gyrase activity and therefore are useful for treating bacterial infections in mammals.

Caspase inhibitors and uses thereof

Pharmaceutical compositions of the amorphous form of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

Gyrase Inhibitors and Uses thereof

PROCESSES AND INTERMEDIARIES

processos e intermediários. a invenção se refere a processos e a compostos úteis para produzir derivados do ácido aspártico modificados, tais como porções aldeídicas do ácido aspártico. derivados do ácido aspártico são úteis para preparar inibidores da caspase e/ou seus pró medicamentos. processes and intermediaries. the invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aldehyde portions of aspartic acid. Aspartic acid derivatives are useful for preparing caspase inhibitors and / or their prodrugs.

Gyrase Inhibitors and Uses thereof

Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound I ), and pharmaceutical compositions thereof.

Process and intermediate products for the preparation of aspartic caspase acetal inhibitors

Un proceso de preparación de un compuesto de beta-amidocarbonilo de fórmula XXX:**Fórmula** que comprende las etapas de: a) hacer reaccionar un compuesto de fórmula XII:**Fórmula** con un compuesto de fórmula XIII:**Fórmula** en presencia de un catalizador de paladio, un ligando de paladio, una base y un disolvente que incluye opcionalmente un catalizador de transferencia de fase y que incluye opcionalmente agua, para producir un compuesto de fórmula XXXI:**Fórmula** en la que: X es un grupo saliente; cada Ra es H, un alquilo opcionalmente sustituido, un arilo opcionalmente sustituido, -CN, -C(O)-Oalquilo o halógeno; cada R2 es independientemente un grupo alifático opcionalmente sustituido, un grupo heterocíclico opcionalmente sustituido o un grupo arilo opcionalmente sustituido; cada R4 es independientemente un alifático opcionalmente sustituido, un heterociclo opcionalmente sustituido, un arilo opcionalmente sustituido, o R2 y R4, junto con los grupos a los que están unidos, forman un anillo heterocíclico de 5 a 8 miembros opcionalmente sustituido; y cada R3 es un resto orgánico. A process of preparing a beta-amidocarbonyl compound of formula XXX: ** Formula ** comprising the steps of: a) reacting a compound of formula XII: ** Formula ** with a compound of formula XIII: ** Formula ** in the presence of a palladium catalyst, a palladium ligand, a base and a solvent that optionally includes a phase transfer catalyst and optionally includes water, to produce a compound of formula XXXI: ** Formula ** in which: X is a leaving group; each Ra is H, an optionally substituted alkyl, an optionally substituted aryl, -CN, -C (O) -Oalkyl or halogen; each R2 is independently an optionally substituted aliphatic group, an optionally substituted heterocyclic group or an optionally substituted aryl group; each R4 is independently an optionally substituted aliphatic, an optionally substituted heterocycle, an optionally substituted aryl, or R2 and R4, together with the groups to ...

Bakterielle gyrase-hemmer sowie deren verwendung

Bakterielle gyrase-hemmer und deren verwendung

Gyrase-inhibitoren und ihre verwendung

Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

Φαρμακευτικες συνθεσεις της αμορφης μορφης ν-[2,4-δις(1,1-διμεθυλαιθυλ)-5-υδροξυφαινυλ]-1,4-διυδρο-4-οξοκινολινο-3-καρβοξαμιδιου

Η παρούσα εφεύρεση αφορά σε στερεάς κατάστασης μορφές του Ν-[2,4-δις(1,1-διμεθυλαιθυλ)-5-υδροξυφαινυλ]-1,4-διυδρο-4-οξοκινολινο-3-καρβοξαμιδίου (Ένωση 1), φαρμακευτικές συνθέσεις αυτού και μεθόδους με αυτό.